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Therapeutic peptides

a technology of peptides and peptides, applied in the field of therapeutic peptides, can solve problems such as weight loss of 0.6 kg

Active Publication Date: 2014-11-06
GLAXOSMITHKLINE INTPROP DEV LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides novel PYY polypeptides with improved therapeutic profiles for the treatment of obesity, diabetes, and other metabolic disorders. These polypeptides can be used alone or in combination with other drugs, such as GLP-1 or exendin-4. The invention also provides nucleic acid molecules and expression vectors for these polypeptides, as well as pharmaceutical compositions and methods of treating metabolic disorders or obesity.

Problems solved by technology

Prevention and treatment of obesity are areas of high unmet medical need, with few medications currently available for chronic weight loss therapy.
Administration of a PYY(3-36) nasal spray reduced daily caloric intake of obese individuals by 2713 kJ, resulting in a weight loss of 0.6 kg over a six-day study period.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

PKPEAPGKDASPEELNRYYASLRHYLNWVTRQRY-NH2 (SEQ ID NO:3)

[0087]Example 1 was prepared on a 35 μmol scale as a white solid using the general method. The molecular mass of the isolated peptide was confirmed by fragment ions (M+3) / 3-1369 amu and (M+4) / 4-1027 amu, which corresponds to a peptide with the parent molecular weight of 4105 amu (ESI-MS, LC / MS Method A). A purity of >90% was determined by C18 HPLC (C18 HPLC Method A, rt=8.90 min) for the isolated peptide (25 mg, as the 8 trifluoroacetic acid salt).

example 2

PKPEAPGKDASPEELNRYYASLRKYLNWLTRQRY-NH2 (SEQ ID NO:4)

[0088]Example 2 was prepared on a 35 μmol scale as a white solid using the general method. The molecular mass of the isolated peptide was confirmed by fragment ions (M+3) / 3-1371 amu and (M+4) / 4-1028 amu, which corresponds to a peptide with the parent molecular weight of 4111 amu (ESI-MS, LC / MS Method A). A purity of >90% was determined by C18 HPLC (C18 HPLC Method A, rt=9.46 min) for the isolated peptide (20 mg, as the 8 trifluoroacetic acid salt).

example 3

PKPEAPGKDASPEELNRYYASLRHYLNWLTRQRY-NH2 (SEQ ID NO:5)

[0089]Example 3 was prepared on a 35 μmol scale as a white solid using the general method. The molecular mass of the isolated peptide was confirmed by fragment ions (M+3) / 3-1374 amu and (M+4) / 4-1031 amu, which corresponds to a peptide with the parent molecular weight of 4120 amu (ESI-MS, LC / MS Method A). A purity of >90% was determined by C18 HPLC (C18 HPLC Method A, rt=9.42 min) for the isolated peptide (16 mg, as the 8 trifluoroacetic acid salt).

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Abstract

The present invention relates to novel analogs of PYY that have an improved therapeutic profile when compared to native human PYY. These novel PYY analogs are useful in the treatment of obesity, diabetes, and other disorders.

Description

FIELD OF THE INVENTION[0001]This invention relates to therapeutic peptides useful in the treatment of obesity and metabolic disorders. More specifically, the invention relates to novel analogs of Peptide YY (PYY) and their use.BACKGROUND OF THE INVENTION[0002]The prevalence of obesity in the United States is increasing, with 35.7% of adults considered obese (BMI≧30) and 68.8% considered overweight (BMI≧25) in 2009-2010. See, for example, Flegal et al. (2012) JAMA 307(5):491-7. Worldwide, over 300 million people are considered obese. Obesity-related diseases, including Type 2 Diabetes Mellitus, hypertension, heart disease, joint disease, and some types of cancer have increased in prevalence as the population has grown heavier.[0003]Prevention of obesity through diet and exercise is of critical importance to control these trends, but once patients become obese, the body's resistance to weight loss can be considerable. Diet and exercise alone may be insufficient to bring about signific...

Claims

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Application Information

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IPC IPC(8): C07K14/575A61K38/26
CPCA61K38/26C07K14/57545A61K38/55A61K38/1709A61P3/04A61P43/00A61P3/10A61K2300/00A61K38/22C07K14/47
Inventor DOCK, STEVEN THOMASCARPENTER, ANDREW JAMESHUNTER, III, ROBERT NEILWU, YULINSRIVASTAVA, VED P.
Owner GLAXOSMITHKLINE INTPROP DEV LTD
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